Cell-surface vimentin positive circulating tumor cells as a diagnostic and prognostic indicator in pediatric sarcoma patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15022-e15022
Author(s):  
Long Dao ◽  
Dristhi Ragoonanan ◽  
Jessica Foglesong ◽  
Izhar Singh Batth ◽  
Wafik Tharwat Zaky ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Surface ◽  
Disease Surveillance ◽  
Disease Status ◽  
Prognostic Indicator ◽  
Adolescent And Young Adult ◽  
Patient Anxiety ◽  
Pediatric Sarcoma ◽  
Prognostic Tests ◽  
Metastatic Sarcoma

e15022 Background: Despite advances in care, the 5 year overall survival for patients with relapsed and or metastatic sarcoma remains as low as < 35%. Currently, there are no biomarkers available to assess disease status in patients with sarcomas and as such, disease surveillance remains only reliant on serial imaging which increases the risk of secondary malignancies and heightens patient anxiety. Methods: Here, we enumerated the cell surface vimentin (CSV+) CTCs in the blood of 92 sarcoma pediatric and adolescent and young adult (AYA) patients. Results: We discovered the CSV+CTC could serve as a possible biomarker of disease with sensitivity of 85.3% and specificity of 75%. Significantly, patients who were deemed to be CSV+ CTC positive were found to have a worse overall survival compared to those who were CSV+ CTC negative (773 days vs 2622 days). Addition of readily available genetic analyses improved the sensitivity in both diagnostic and prognostic tests. Conclusions: Our findings indicate that CSV+ CTCs have both diagnostic and prognostic value and can possibly serve as a measure of disease burden.

scholarly journals Prognostic Value of Cell-Surface Vimentin-Positive CTCs in Pediatric Sarcomas

2021 ◽  
Vol 11 ◽  
Author(s):  
Long Dao ◽  
Dristhi Ragoonanan ◽  
Izhar Batth ◽  
Arun Satelli ◽  
Jessica Foglesong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Surface ◽  
Disease Surveillance ◽  
Prognostic Value ◽  
Disease Status ◽  
Adolescent And Young Adult ◽  
Molecular Testing ◽  
Patient Anxiety ◽  
Pediatric Sarcomas ◽  
Prognostic Tests

BackgroundDespite advances in care, the 5 year overall survival for patients with relapsed and or metastatic sarcoma remains as low as &lt; 35%. Currently, there are no biomarkers available to assess disease status in patients with sarcomas and as such, disease surveillance remains reliant on serial imaging which increases the risk of secondary malignancies and heightens patient anxiety.MethodsHere, for the first time reported in the literature, we have enumerated the cell surface vimentin (CSV+) CTCs in the blood of 92 sarcoma pediatric and adolescent and young adult (AYA) patients as a possible marker of disease.ResultsWe constructed a ROC with an AUC of 0.831 resulting in a sensitivity of 85.3% and a specificity of 75%. Additionally, patients who were deemed to be CSV+ CTC positive were found to have a worse overall survival compared to those who were CSV+ CTC negative. We additionally found the use of available molecular testing increased the accuracy of our diagnostic and prognostic tests.ConclusionsOur findings indicate that CSV+ CTCs have prognostic value and can possibly serve as a measure of disease burden.

scholarly journals Diagnostic and Prognostic Value of Cell-Surface Vimentin-Positive Circulating Tumor Cells in Pediatric Sarcoma Patients

2021 ◽  
Author(s):  
Long Dao ◽  
Dristhi Ragoonanan ◽  
Izhar Batth ◽  
Arun Satelli ◽  
Jessica Foglesong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Surface ◽  
Disease Surveillance ◽  
Prognostic Value ◽  
Disease Status ◽  
Adolescent And Young Adult ◽  
Molecular Testing ◽  
Patient Anxiety ◽  
Prognostic Tests ◽  
Diagnostic And Prognostic Value

Abstract Background Despite advances in care, the 5 year overall survival for patients with relapsed and or metastatic sarcoma remains as low as < 35%. Currently, there are no biomarkers available to assess disease status in patients with sarcomas and as such, disease surveillance remains reliant on serial imaging which increases the risk of secondary malignancies and heightens patient anxiety. Methods Here, for the first time reported in the literature, we have enumerated the cell surface vimentin (CSV+) CTCs in the blood of 92 sarcoma pediatric and adolescent and young adult (AYA) patients as a possible marker of disease. Results We constructed a ROC with an AUC of 0.831 resulting in a sensitivity of 85.3% and a specificity of 75%. Additionally, patients who were deemed to be CSV + CTC positive were found to have a worse overall survival compared to those who were CSV + CTC negative. We additionally found the use of available molecular testing increased the accuracy of our diagnostic and prognostic tests. Conclusions Our findings indicate that CSV + CTCs have both diagnostic and prognostic value and can possibly serve as a measure of disease burden.

scholarly journals Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1612
Author(s):  
Julie Earl ◽  
Emma Barreto ◽  
María E. Castillo ◽  
Raquel Fuentes ◽  
Mercedes Rodríguez-Garrote ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Somatic Mutation ◽  
Disease Status ◽  
Clinical Analysis ◽  
Cytotoxic Agents ◽  
Disease Stage ◽  
Ductal Adenocarcinoma ◽  
Familial Pancreatic Cancer ◽  
Circulating Free Dna

Pancreatic ductal adenocarcinoma (PDAC) presents many challenges in the clinic and there are many areas for improvement in diagnostics and patient management. The five-year survival rate is around 7.2% as the majority of patients present with advanced disease at diagnosis that is treatment resistant. Approximately 10–15% of PDAC cases have a hereditary basis or Familial Pancreatic Cancer (FPC). Here we demonstrate the use of circulating free DNA (cfDNA) in plasma as a prognostic biomarker in PDAC. The levels of cfDNA correlated with disease status, disease stage, and overall survival. Furthermore, we show for the first time via BEAMing that the majority of hereditary or familial PDAC cases (around 84%) are negative for a KRAS somatic mutation. In addition, KRAS mutation negative cases harbor somatic mutations in potentially druggable genes such as KIT, PDGFR, MET, BRAF, and PIK3CA that could be exploited in the clinic. Finally, familial or hereditary cases have a longer overall survival compared to sporadic cases (10.2 vs. 21.7 months, respectively). Currently, all patients are treated the same in the clinic with cytotoxic agents, although here we demonstrate that there are different subtypes of tumors at the genetic level that could pave the way to personalized treatment.

scholarly journals Cancer antigen 125 is associated with disease status in uterine carcinosarcoma

Rare Tumors ◽  
2019 ◽  
Vol 11 ◽  
pp. 203636131988415
Author(s):  
Malcolm Strachan Ross ◽  
Chelsea Kilpatrick Chandler ◽  
Koji Matsuo ◽  
John Austin Vargo ◽  
Esther Elishaev ◽  
...  
Keyword(s):  
Overall Survival ◽  
Uterine Cancer ◽  
Disease Status ◽  
Post Treatment ◽  
Uterine Carcinosarcoma ◽  
Cancer Antigen 125 ◽  
Cancer Antigen ◽  
Time Points ◽  
Potential Biomarker ◽  
Significant Difference

Uterine carcinosarcoma is a rare and aggressive tumor with poor outcomes. Cancer antigen 125 is routinely used to track the disease course of ovarian cancer and has been suggested as a biomarker in other aggressive forms of uterine cancer. We sought to characterize cancer antigen 125 as a potential biomarker of disease status in uterine carcinosarcoma. Clinical and pathological data were abstracted for patients who had surgical staging for a pathologically confirmed uterine carcinosarcoma at our institution from January 2000 to March 2014. Non-parametric tests were used to compare changes in cancer antigen 125. Elevated cancer antigen 125 (>35 U/mL) as a predictor of survival was assessed via Kaplan–Meier curves. Among the 153 patients identified, 66 patients had at least one paired measure of cancer antigen 125 drawn preoperatively, post-treatment, or at the time of disease recurrence, and 19 patients had cancer antigen–125 levels at all three time points. Analysis of the 51 patients with both preoperative and post-treatment values found a significant drop in cancer antigen 125 ( p < 0.001). Among the 30 patients who had end-of-treatment and recurrence levels, a significant increase was noted ( p = 0.001). There was no significant difference in cancer antigen–125 levels preoperatively compared to at recurrence among the 23 patients with levels at both time-points ( p = 0.99). Elevated preoperative cancer antigen 125 was not associated with overall survival ( p = 0.12); elevated post-treatment cancer antigen 125 was associated with a worse overall survival ( p < 0.001). Based on this dataset, there seems to be utility in trending a cancer antigen–125 level in patients with uterine carcinosarcoma. A cancer antigen–125 level could predict recurrence and provide prognostic information regarding survival.

scholarly journals HLA allele-specific expression loss in tumors can shorten survival and hinder immunotherapy

2020 ◽  
Author(s):  
Ioan Filip ◽  
Rose Orenbuch ◽  
Junfei Zhao ◽  
Gulam Manji ◽  
Evangelina López de Maturana ◽  
...  
Keyword(s):  
Overall Survival ◽  
Human Leukocyte ◽  
Prognostic Indicator ◽  
Cancer Prognosis ◽  
Sequencing Data ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Allele Specific ◽  
Tumor Types ◽  
Expression Loss

AbstractEfficient presentation of aberrant peptide fragments by the human leukocyte antigen class I (HLA-I) genes is necessary for immune detection and killing of cancer cells. Patient HLA-I genotypes are known to impact the efficacy of cancer immunotherapy, and the somatic loss of HLA-I heterozygosity has been established as a factor in immune evasion. While global deregulated expression of HLA-I has been reported in different tumor types, the role of HLA-I allele-specific expression loss – that is, the preferential RNA expression loss of specific HLA-I alleles – has not been fully characterized in cancer. In the present study, we quantified HLA-I allele-specific expression (ASE) across eleven TCGA tumor types using a novel method from input RNA and whole-exome sequencing data. Allele-specific loss in at least one of the three HLA-I genes (ASE loss) was pervasive and associated to worse overall survival across tumor types, including pancreatic adenocarcinomas, prostate carcinomas and glioblastomas, among others. In particular, our analysis shows that detection of neoantigens with binding affinity to the specific HLA-I genes subject to ASE loss was a top prognostic indicator of overall survival. Additionally, we found that ASE loss hindered immunotherapy in retrospective analyses. Together, these results highlight the prevalence of HLA-I ASE loss – a previously uncharacterized phenomenon in cancer – and provide initial evidence of its clinical significance in cancer prognosis and immunotherapy treatment.

scholarly journals Increased GOLM1 Expression Independently Predicts Unfavorable Overall Survival and Recurrence-Free Survival in Lung Adenocarcinoma

2018 ◽  
Vol 25 (1) ◽  
pp. 107327481877800 ◽  
Author(s):  
Xi Liu ◽  
Lei Chen ◽  
Tao Zhang
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Methylation Status ◽  
Lung Squamous Cell Carcinoma ◽  
Prognostic Indicator ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Recurrence Free Survival ◽  
Free Survival

Golgi membrane protein 1 (GOLM1) is a transmembrane glycoprotein of the Golgi cisternae, which is implicated in carcinogenesis of multiple types of cancer. In this study, using data from the Gene Expression Omnibus and The Cancer Genome Atlas, we compared the expression of GOLM1 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and studied its prognostic value in terms of overall survival (OS) and recurrence-free survival (RFS) in these 2 subtypes of non-small cell lung cancer (NSCLC). Results showed that GOLM1 was significantly upregulated in both LUAD and LUSC tissues compared to the normal controls. However, GOLM1 expression was higher in LUAD tissues than in LUSC tissues. More importantly, using over 10 years’ survival data from 502 patients with LUAD and 494 patients with LUSC, we found that high GOLM1 expression was associated with unfavorable OS and RFS in patients with LUAD, but not in patients with LUSC. The following univariate and multivariate analyses confirmed that increased GOLM1 expression was an independent prognostic indicator of poor OS (hazard ratio [HR]: 1.30, 95% confidence interval [CI]: 1.11-1.54, P = .002) and RFS (HR: 1.37, 95% CI: 1.14-1.64, P = .001) in patients with LUAD. Of 511 cases with LUAD, 248 (48.5%) had heterozygous loss (−1), while 28 (5.5%) of 511 cases with LUAD had low-level copy gain (+1). In addition, we also found that the methylation status of 1 CpG site (chr9: 88,694,942-88,694,944) showed a weak negative correlation with GOLM1 expression (Pearson r = −0.25). Based on these findings, we infer that GOLM1 might serve as a valuable prognostic biomarker in LUAD, but not in LUSC. In addition, DNA copy number alterations and methylation might be 2 important mechanisms of dysregulated GOLM1 in LUAD.

scholarly journals ATP binding cassette subfamily B member 9 (ABCB9) is a prognostic indicator of overall survival in ovarian cancer

Medicine ◽  
2019 ◽  
Vol 98 (19) ◽  
pp. e15698 ◽  
Author(s):  
Lin Hou ◽  
Xueying Zhang ◽  
Yan Jiao ◽  
Yanqing Li ◽  
Yuechen Zhao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Prognostic Indicator ◽  
Atp Binding ◽  
Atp Binding Cassette

scholarly journals Long-term remission of Philadelphia chromosome–positive acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation from matched sibling donors: a 20-year experience with the fractionated total body irradiation–etoposide regimen

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 903-909 ◽  
Author(s):  
Ginna G. Laport ◽  
Joseph C. Alvarnas ◽  
Joycelynne M. Palmer ◽  
David S. Snyder ◽  
Marilyn L. Slovak ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Total Body Irradiation ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Disease Status ◽  
Matched Sibling ◽  
Total Body

Abstract Allogeneic hematopoietic cell transplantation (HCT) is the only known curative modality for patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). Sixty-seven patients with HLA-matched sibling donors received fractionated total body irradiation (FTBI) and high-dose VP16, whereas 11 patients received FTBI/VP16/cyclophosphamide, and 1 patient received FTBI/VP16/busulfan. The median age was 36 years. At the time of HCT, 49 patients (62%) were in first complete remission (CR1) and 30 patients (38%) were beyond CR1 (> CR1). The median follow-up was 75 months (range, 14-245 months). The 10-year overall survival for the CR1 and beyond CR1 patients was 54% and 29% (P = .01), respectively, and event-free survival was 48% and 26% (P = .02), respectively. There was no significant difference in relapse incidence (28% vs 41%, P = .28), but nonrelapse mortality was significantly higher in the beyond CR1 patients, (31% vs 54%, P = .03, respectively). By univariate analysis, factors affecting event-free and overall survival were white blood cell count at diagnosis (< 30 × 109/L vs > 30 × 109/L) and disease status (CR1 vs > CR1). The median time to relapse for CR1 and for beyond CR1 patients was 12 months and 9 months, respectively. Our results indicate that FTBI/VP16 with or without cyclophosphamide confers long-term survival in Ph+ ALL patients and that disease status at the time of HCT is an important predictor of outcome.

Using pharmacy data to identify those with chronic conditions in Emilia Romagna, Italy

2005 ◽  
Vol 10 (4) ◽  
pp. 232-238 ◽  
Author(s):  
Vittorio Maio ◽  
Elaine Yuen ◽  
Carol Rabinowitz ◽  
Daniel Louis ◽  
Masahito Jimbo ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Disease Surveillance ◽  
Chronic Conditions ◽  
Chronic Condition ◽  
External Validation ◽  
Disease Status ◽  
Respiratory Illness ◽  
Gastrointestinal Diseases ◽  
Surveillance Study ◽  
Pharmacy Data

Background and objectives: Automated pharmacy data have been used to develop a measure of chronic disease status in the general population. The objectives of this project were to refine and apply a model of chronic disease identification using Italian automated pharmacy data; to describe how this model may identify patterns of morbidity in Emilia Romagna, a large Italian region; and to compare estimated prevalence rates using pharmacy data with those available from a 2000 Emilia Romagna disease surveillance study. Methods: Using the Chronic Disease Score, a list of chronic conditions related to the consumption of drugs under the Italian pharmaceutical dispensing system was created. Clinical review identified medication classes within the Italian National Therapeutic Formulary that were linked to the management of each chronic condition. Algorithms were then tested on pharmaceutical claims data from Emilia Romagna for 2001 to verify the applicability of the classification scheme. Results: Thirty-one chronic condition drug groups (CCDGs) were identified. Applying the model to the pharmacy data, approximately 1.5 million individuals (37.1%) of the population were identified as having one or more of the 31 CCDGs. The 31 CCDGs accounted for 77% (E556 million) of 2001 pharmaceutical expenditures. Cardiovascular diseases, rheumatological conditions, chronic respiratory illness, gastrointestinal diseases and psychiatric diseases were the most frequent chronic conditions. External validation comparing rates of the diseases found through using pharmacy data with those of a 2000 Emilia Romagna disease surveillance study showed similar prevalence of illness. Conclusions: Using Italian automated pharmacy data, a measure of population-based chronic disease status was developed. Applying the model to pharmaceutical claims from Emilia Romagna 2001, a large proportion of the population was identified as having chronic conditions. Pharmacy data may be a valuable alternative to survey data to assess the extent to which large populations are affected by chronic conditions.

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